Development of cell-expressed and virion-incorporated CCR5-targeted vaccine.
Our previous study demonstrated that the immunization with a cycloimmunogen derived from extracellular loop-2 (ECL-2) of CCR5 (cDDR5) attenuated acute phase of CCR5-tropic simian-human immunodeficiency virus (SHIV)(SF162P3) replication in vivo. Although the study showed that the antisera raised against cDDR5 reacted with cell-expressed CCR5, we have not yet demonstrated whether the antisera can react with virion-incorporated CCR5. Here, we show that rhesus cDDR5 (rcDDR5)-specific antibodies react with not only cell-expressed but also virion-incorporated simian CCR5s (siCCR5s), but may predominantly exert their inhibitory effects on simian immunodeficiency virus (SIV) infection by the binding of cell-expressed rather than virion-incorporated CCR5s. These results suggest that the virion-incorporated CCR5 may contribute to the reactivation of the anti-rcDDR5 antibody-producing B-cells by SIV particles after rcDDR5 immunization, although the binding of anti-rcDDR5 antibody to virion-incorporated CCR5 results in a partial inhibitory effect on SIV infection.
Misumi
Shogo
S
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan. Electronic address: misumi@gpo.kumamoto-u.ac.jp.
Eto
Ayumi
A
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Mitsumata
Ryotarou
R
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Yamada
Masanori
M
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Takamune
Nobutoki
N
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Shoji
Shozo
S
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan; Kumamoto Health Science University, Kumamoto 861-5598, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006678:HIV / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D010455:Peptides; D019713:Receptors, CCR5; D014765:Viral Vaccines